Volume 7. Issue 6. Pages 685-814. 2012 ISSN 1934-578X (printed); ISSN 1555-9475 (online)

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NPC Natural Product Communications

EDITOR-IN-CHIEF

DR. PAWAN K AGRAWAL Natural Product Inc. 7963, Anderson Park Lane, Westerville, Ohio 43081, USA agrawal@naturalproduct.us

EDITORS

PROFESSOR ALEJANDRO F. BARRERO Department of Organic Chemistry, University of Granada, Campus de Fuente Nueva, s/n, 18071, Granada, Spain afbarre@ugr.es

PROFESSOR ALESSANDRA BRACA Dipartimento di Chimica Bioorganicae Biofarmacia, Universita di Pisa, via Bonanno 33, 56126 Pisa, Italy braca@farm.unipi.it

PROFESSOR DEAN GUO State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100083, China gda5958@163.com

PROFESSOR YOSHIHIRO MIMAKI School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Horinouchi 1432-1, Hachioji, Tokyo 192-0392, Japan mimakiy@ps.toyaku.ac.jp

PROFESSOR STEPHEN G. PYNE Department of Chemistry University of Wollongong Wollongong, New South Wales, 2522, Australia spyne@uow.edu.au

PROFESSOR MANFRED G. REINECKE Department of Chemistry, Texas Christian University, Forts Worth, TX 76129, USA m.reinecke@tcu.edu

PROFESSOR WILLIAM N. SETZER Department of Chemistry The University of Alabama in Huntsville Huntsville, AL 35809, USA wsetzer@chemistry.uah.edu

PROFESSOR YASUHIRO TEZUKA Institute of Natural Medicine Institute of Natural Medicine, University of Toyama, 2630-Sugitani, Toyama 930-0194, Japan tezuka@inm.u-toyama.ac.jp

PROFESSOR DAVID E. THURSTON Department of Pharmaceutical and Biological Chemistry, The School of Pharmacy, University of London, 29-39 Brunswick Square, London WC1N 1AX, UK david.thurston@pharmacy.ac.uk

ADVISORY BOARD Prof. Berhanu M. Abegaz Gaborone, Botswana

Prof. Viqar Uddin Ahmad Karachi, Pakistan

Prof. Øyvind M. Andersen Bergen, Norway

Prof. Giovanni Appendino Novara, Italy

Prof. Yoshinori Asakawa Tokushima, Japan

Prof. Lee Banting Portsmouth, U.K.

Prof. Julie Banerji Kolkata, India

Prof. Anna R. Bilia Florence, Italy

Prof. Maurizio Bruno Palermo, Italy

Prof. César A. N. Catalán Tucumán, Argentina

Prof. Josep Coll Barcelona, Spain

Prof. Geoffrey Cordell Chicago, IL, USA

Prof. Ana Cristina Figueiredo Lisbon, Portugal

Prof. Cristina Gracia-Viguera Murcia, Spain

Prof. Duvvuru Gunasekar Tirupati, India

Prof. Kurt Hostettmann Lausanne, Switzerland

Prof. Martin A. Iglesias Arteaga Mexico, D. F, Mexico

Prof. Jerzy Jaroszewski Copenhagen, Denmark

Prof. Leopold Jirovetz Vienna, Austria

Prof. Karsten Krohn Paderborn, Germany

Prof. Hartmut Laatsch Gottingen, Germany

Prof. Marie Lacaille-Dubois Dijon, France

Prof. Shoei-Sheng Lee Taipei, Taiwan

Prof. Francisco Macias Cadiz, Spain

Prof. Imre Mathe Szeged, Hungary

Prof. Joseph Michael Johannesburg, South Africa

Prof. Ermino Murano Trieste, Italy

Prof. M. Soledade C. Pedras Saskatoon, Canada

Prof. Luc Pieters Antwerp, Belgium

Prof. Peter Proksch Düsseldorf, Germany

Prof. Phila Raharivelomanana Tahiti, French Polynesia

Prof. Luca Rastrelli Fisciano, Italy

Prof. Monique Simmonds Richmond, UK

Prof. John L. Sorensen Manitoba, Canada

Prof. Valentin Stonik Vladivostok, Russia

Prof. Winston F. Tinto Barbados, West Indies

Prof. Sylvia Urban Melbourne, Australia

Prof. Karen Valant-Vetschera Vienna, Austria

HONORARY EDITOR

PROFESSOR GERALD BLUNDEN The School of Pharmacy & Biomedical Sciences,

University of Portsmouth, Portsmouth, PO1 2DT U.K.

axuf64@dsl.pipex.com

Unusual Nitrogenous Derivatives from Alstonia Shin-Jowl Tana, G. Subramaniamb, Noel F. Thomasa and Toh-Seok Kama,* aDepartment of Chemistry, University of Malaya, 50603 Kuala Lumpur, Malaysia

bSchool of Chemical and Life Sciences, Nanyang Polytechnic, 180 Ang Mo Kio Ave 8, Singapore 569830 tskam@um.edu.my

Received: December 21st, 2011; Accepted: February 23rd, 2012

Five new nitrogenous compounds were isolated from the Malayan Alstonia angustifolia and their structures determined based on interpretation of spectroscopic data. Keywords: Nitrogenous compounds, Alkaloids, Alstonia.

The genus Alstonia represents a rich source of alkaloids, including those with useful biological activities. In addition to indole and bisindole alkaloids, plants of this genus have also yielded some unusual nitrogenous metabolites. For instance, we recently reported the presence of unusual alkaloid-pyrrole, alkaloid-pyrone, and alkaloid-carbamic acid adducts {alstopirocine (1), pleiomaltinine (2), and pleiomalicine (3), respectively} from A. angustifolia, and proposed possible biogenetic pathways for their formation [1]. An earlier study of A. angustifolia and A. macrophylla yielded the unusual nitrogenous compounds, angustimaline (4) [2], and the related compound, angustimalal (5) [3], respectively. We report further isolation of five new compounds (angustimalines AE, 610) related to 4 and 5 from the bark extract of A. angustifolia. Previously, we isolated angustimaline (4), as a pure compound, from the stem-bark extract of A. angustifolia [2]. In the present study, however, angustimaline (4) was isolated together with its isomer, angustimaline A (6), as an inseparable mixture, which co-eluted in column chromatography, and which proved resistant to further attempts at resolution by either chromatography or fractional crystallization. The ESIMS showed a pseudomolecular ion at m/z 238, which analyzed for C13H19NO3. The NMR data indicated the presence of a mixture of compounds corresponding to the non-indole portion of the type-A (aldehyde) and type-B (ketone) macrolines [4], with the type-B isomer (ketone, 4) predominating over the type-A isomer (aldehyde, 6), by a four-fold excess. Most of the hydrogen signals of compound 4 and the corresponding signals of compound 6 were coincident in the 1H NMR spectrum (Table 1), except for the signals of H-13 (vinylic-H for 4, aldehyde-H for 6), which were clearly distinguishable, while the H-9 signals of both compounds are only partially resolved. The same phenomenon was also observed in the 13C NMR spectrum (Table 2), where the majority of the corresponding carbon signals of both compounds were coincident, with the exception of C-10, C-11, C-12, and C-13. This behavior has been previously seen in the case of the type-A and type-B macroline alkaloids, such as alstonerinal (11) and alstonerine (12) [5], N(4)-demethylalstonerinal and N(4)-demethylalstonerine [6], 6-oxoalstophyllal and 6-oxoalstophylline [7], alstophyllal and alstophylline [6] (type-A major), alstonal and alstonisine [8,9] (separated by fractional crystallization), Nb-demethylalstophyllal oxindole and Nb-demethylalstophylline oxindole [9] (separated by fractional crystallization), and N(1)-demethylalstonal and N(1)-demethylalstonisine [8]. These

compounds tend to co-elute during isolation and are frequently obtained as a mixture, usually with the type-B macroline form (ketone) predominating. Since the majority of the signals in the 1H and 13C NMR spectra of both type-A and -B macroline alkaloids are overlapped, the presence of the minor type-A macroline (aldehyde) may sometimes escape detection. Not all compounds of this type are obtained as non-resolvable mixtures, some, such as 16-hydroxyalstonal and 16-hydroxyalstonisine [7], 16-hydroxy-N(4)-demethylalstophyllal oxindole and 16-hydroxy-N(4)-demethyl-alstophylline oxindole [7,10], are resolvable and are obtained as pure compounds by chromatography. As in the previous pair of compounds (4 and 6), angustimalines B (7) and C (8) were also isolated as an inseparable mixture, which resisted further fractionation, with the type-B isomer (8) predominating by a five-fold excess. The UV spectrum showed an absorption maximum at 260 nm, while the IR spectrum showed bands for hydroxyl (3391 cm-1), ,-unsaturated carbonyl and enol ether (1614, 1650 cm-1) functionalities. The EIMS showed the molecular ion at m/z 237 (isomeric with 4 and 6), while the fragment ion observed at m/z 193 (base peak) can be attributed to the loss of CH2=CHOH. As in the case of 4 and 6, most of the hydrogen signals of 7 (type-A) and the corresponding signals of 8 (type-B) were coincident in the 1H NMR spectrum (Table 1), except for the signals of H-13 (aldehyde-H for 7, vinylic-H for 8), which were clearly distinguishable, while the H-6 and H-9 signals of both compounds were only partially resolved. In the 13C NMR spectrum (Table 2), the majority of the corresponding signals were coincident, except for the signals due to C-10, C-11, C-12, and C-13. In the case of angustimaline (4), the relative configuration at C-4 was established from the observed H-4/H-7 reciprocal NOE, which indicated -OH substitution at C-4 [2] (Figure 1). In the case of 7 and 8, the observed NOEs for H-4/H-3, N-Me, and the absence of NOEs for H-4/H-7, indicated -OH substitution at C-4 (Figure 2). Compounds 7 and 8 are, therefore, the C-4 epimers of compounds 6 and 4, respectively. Another pair of nitrogenous compounds isolated as a mixture was angustimalines D (9) and E (10), with the type-B form, 10, obtained as the major isomer in 5-fold excess. In this case, however, partial resolution of the mixture, resulting in a pure sample of 10 with a

NPC Natural Product Communications 2012 Vol. 7 No. 6

739 - 742

740 Natural Product Communications Vol. 7 (6) 2012 Tan et al.

Table 1: 1H NMR spectroscopic data () for 4 and 610 (400 MHz, CDCl3)

a

H 4 6 7 8 9 10 2 3.28 br d (5) 3.28 br d (5) 2.98 m 2.98 m 3.47 br d (7) 3.47 br d (7) 3 2.13 dd (14, 7) 2.13 dd (14, 7) 1.59 dd (14, 3.6) 1.59 dd (14, 3.6) 2.13 d (19) 2.14 d (19) 3 2.29 ddd (14, 7, 3) 2.29 ddd (14, 7, 3) 2.79 ddd (14, 10.5, 7.3) 2.79 ddd (14, 10.5, 7.3) 2.74 dd (19, 7) 2.74 dd (19, 7) 4 4.59 dd (7, 3) 4.59 dd (7, 3) 4.79 ddd (10.5, 5.8, 3.9) 4.79 ddd (10.5, 5.8, 3.9) 2.85 m 2.85 m 5 3.02 m 3.02 m 3.01 m 3.01 m 1.63 td (13, 3) 1.64 td (13, 3) 5 2.30 m 2.31 ddd (13, 6, 4) 6 1.38 td (12.9, 3) 1.37 td (13, 3) 1.43 ddd (13, 11.6, 3.2) 1.43 ddd (13, 11.6, 3.2) 6 2.02 ddd (13, 6, 3) 2.05 ddd (13, 6, 3) 2.37 ddd (13, 5.7, 2.8) 2.33 ddd (13, 5.7, 2.8) 2.82 m 2.82 m 7 2.54 m 2.54 m 3.09 dt (11.6, 5.7) 3.09 dt (11.6, 5.7) 1.92 m 1.92 m 8 1.61 m 1.61 m 1.78 m 1.78 m 4.23 ddd (11, 4, 2) 4.20 ddd (11, 4, 2) 8 4.53 t (11) 4.48 t (11) 9 4.08 ddd (11, 4, 1.5) 4.11 ddd (11, 4, 1.5) 4.12 ddd (11, 4, 1.7) 4.10 ddd (11, 4, 1.7) 2.20 s 2.17 s 9 4.28 t (11) 4.31 t (11) 4.28 t (11) 4.35 t (11) 10 2.17 s 2.17 s 2.19 s 2.19 s 12 9.76 s 7.56 s13 7.54 s 9.73 s 9.78 s 7.55 s N-Me 2.49 s 2.49 s 2.25 s 2.25 s 2.32 s 2.32 s a Assignments based on COSY, HMQC, HMBC and NOE.

Figure 1: Selected NOEs of 4 (R = Me).

Figure 2: Selected NOEs of 8 (R = Me).

mixed fraction containing enriched 9, was eventually achieved by normal phase HPLC (SiO2, EtOAc/hexanes) using a deactivated column. Angustimaline E (10) was obtained as a light yellowish oil. The UV spectrum showed a maximum at 254 nm (log ε 3.90), while the IR

spectrum showed bands for ,-unsaturated carbonyl and enol ether (1651, 1615 cm-1) functions. The EIMS of 10 showed a molecular ion at m/z 207 (base peak), the odd mass consistent with the presence of a single nitrogen. Other significant fragment peaks were observed at m/z 192 (MCH3) and 164 (MCOCH3). HREIMS measurements gave the formula C12H17NO2. COSY and HMQC experiments showed the presence of the partial structure NCHCH2CHCH2CHCHCH2, corresponding to the C-2C-3C-4C-5C-6C-7C-8 unit. The 1H NMR spectral data (Table 1) showed the presence of a low field one H singlet at δ 7.56, attributed to an olefinic-H associated with a vinyl ether function, an N-methyl singlet at δ 2.32, and a methyl ketone singlet at δ 2.17. The 13C NMR spectrum (Table 2) indicated the presence of an ,-unsaturated ketone (δ 195.5), two olefinic carbons associated with an enol ether function (δ 120.6 and 157.5), and an oxymethylene at δ 66.8. The NOE interactions observed for NMe/H-2, H-3, H-4; H-5/H-4, H-8 are in complete agreement with the relative configuration shown in 10 (Figure 3).

Nitrogenous compounds from Alstonia angustifolia Natural Product Communications Vol. 7 (6) 2012 741

Figure 3: Selected NOEs of 10. Table 2: 13C NMR spectroscopic data () for 4 and 610 (100 MHz, CDCl3)

a.

C 4 6 7 8 9 10 2 64.2 64.2 62.0 62.0 60.3 60.33 39.0 39.0 36.1 36.1 37.2 37.2 4 76.1 76.0 70.8 70.8 69.0 69.0 5 71.0 71.0 64.6 64.6 32.2 32.2 6 33.5 33.1 30.0 30.4 22.9 23.3 7 23.4 23.0 23.0 23.4 36.8 36.8 8 37.3 37.3 38.0 38.0 66.8 66.8 9 67.1 67.4 68.0 67.7 16.5 25.0 10 25.0 16.5 16.6 25.2 171.0 195.5 11 196.4 171.5 171.0 196.5 120.6 120.6 12 121.2 117.6 118.2 121.8 188.7 157.5 13 157.7 189.3 189.5 157.2 N-Me 43.1 43.1 42.2 42.2 42.2 42.3

a Assignments based on HMQC and HMBC. As in the case of the previous pairs of compounds, the 1H NMR and 13C NMR data for the aldehyde or type-A isomer, 9 (Tables 1 and 2), can be extracted from the NMR spectra of the mixture containing enriched 9 obtained from HPLC. As before, most of the signals in the 1H NMR spectrum are either overlapped or coincident, except for the signals due to H-9 (methyl) and H-12 (aldehyde-H for 9, vinylic-H for 10), while the signals for H-8 are only partially resolved. The 13C NMR spectrum showed overlap of the corresponding pairs for most of the signals except for the signals due to C-9, C-10, and C-12. The origin of these compounds remains enigmatic, although a simple assumption is that they are probably derived from fragmentation of a macroline type precursor. It is also likely that the type-A and type-B isomers derive from ring closure of a common precursor (e.g. 11 and 12 from 13). Experimental

General: Optical rotations were determined on a JASCO P-1020 automatic digital polarimeter. IR spectra were recorded on a Perkin-Elmer RX1 FT-IR spectrophotometer. UV spectra were obtained on a Shimadzu UV-3101PC spectrophotometer. EIMS and HREIMS were obtained at Organic Mass Spectrometry, Central Science Laboratory, University of Tasmania, Tasmania, Australia. HRESIMS were recorded on an Agilent 6530 Q-TOF mass spectrometer. HPLC was carried out using a Waters 600 multisolvent delivery system equipped with a Waters 486 UV detector. 1H and 13C NMR spectra were recorded in CDCl3 using TMS as an internal standard on a JEOL JNM-LA 400 spectrometer at 400 and 100 MHz, respectively. Plant material: Plant material was collected in Johor, Malaysia (June 2003) and identified by Prof. K. M. Wong (Institute of Biological Sciences, University of Malaya, Malaysia) and Dr Richard C. K. Chung (Forest Research Institute, Malaysia). Herbarium voucher specimens (K665) are deposited at the Herbarium of the University of Malaya. Extraction and isolation: Extraction of the stem-bark (8 kg) and partitioning of the concentrated EtOH extracts with dilute hydrochloric acid (5%) were carried out as described in detail

elsewhere [11]. The alkaloids were isolated by initial column chromatography on silica gel using CHCl3 with increasing proportions of MeOH, followed by rechromatography of the appropriate partially resolved fractions using centrifugal preparative TLC. Solvent systems used for centrifugal preparative TLC were Et2O, Et2O/MeOH (100:1) (NH3-saturated), Et2O/MeOH (25:1) (NH3-saturated), and CHCl3/hexanes (NH3-saturated) (2:1). Final purification of a mixture of compounds 9 and 10 required HPLC (Spherisorb® column, 5μm, 10 x 250 mm). The column was eluted with EtOAc/hexanes (isocratic: EtOAc/hexanes (1:1), at a flow rate of 3 mL/min to afford pure 10, with a mixed fraction containing enriched 9. The yields (mg kg-1) of the alkaloids were as follows: 4 (0.64), 6 (0.16), 7 (0.25), 8 (1.25), 9 (0.16), and 10 (3.0). Angustimaline (4) and angustimaline A (6) Light yellowish oil. IR (dry film) max: 3412, 1643, 1614 cm-1. UV/Vis λmax (EtOH) nm (log ε): 258 (4.16). 1H NMR (400 MHz, CDCl3): Table 1. 13C NMR (100 MHz, CDCl3): Table 2. HRMS-ESI: m/z [M + H]+ calcd for C13H19NO3: 238.1438; found: 238.1435. Angustimaline B (7) and angustimaline C (8) Light yellowish oil. IR (dry film) max: 3391, 1650, 1614 cm-1. UV/Vis λmax (EtOH) nm (log ε): 260 (3.18). 1H NMR (400 MHz, CDCl3): Table 1. 13C NMR (100 MHz, CDCl3): Table 2. MS (EI): m/z (%) = 237 [M]+ (41), 193 [MC2=CHOH]+ (100), 165 (28), 150 [MC2=CHOHC3CO]+ (42), 132 (20), 108 (28), 94 (43), 82 (31), 70 (37), 43 (33). HRMS-EI: m/z [M]+ calcd for C13H19NO3: 237.1365; found: 237.1365. Angustimaline D (9) (obtained as major compound in mixture with 10 after HPLC) Light yellowish oil. IR (dry film) max: 1651, 1615 cm-1.

UV/Vis λmax (EtOH) nm (log ε): 254 (3.90). 1H NMR (400 MHz, CDCl3): Table 1. 13C NMR (100 MHz, CDCl3): Table 2. MS (EI): m/z (%) = 207 [M]+ (100), 192 (46), 179 (22), 150 (9), 136 (15), 122 (11), 110 (19), 94 (9), 82 (42), 68 (7), 57 (15), 42 (36). HRMS-EI: m/z [M]+ calcd for C12H17NO2: 207.1259; found: 207.1260. Angustimaline E (10) Light yellowish oil. [α]D

25: +58 (c 0.21, CHCl3). IR (dry film) max: 1651, 1615 cm-1.

UV/Vis λmax (EtOH) nm (log ε): 254 (3.90). 1H NMR (400 MHz, CDCl3): Table 1. 13C NMR (100 MHz, CDCl3): Table 2. MS (EI): m/z (%) = 207 [M]+ (100), 192 (46), 179 (22), 164 (73), 150 (9), 136 (15), 122 (11), 110 (19), 94 (9), 82 (42), 68 (7), 57 (15), 42 (36). HRMS-EI: m/z [M]+ calcd for C12H17NO2: 207.1259; found: 207.1260. Acknowledgments - We thank the University of Malaya and MOHE Malaysia (HIR Grants) for financial support.

742 Natural Product Communications Vol. 7 (6) 2012 Tan et al.

References

[1] Tan SJ, Choo YM, Thomas NF, Robinson WT, Komiyama K, Kam TS. (2010) Unusual indole alkaloid–pyrrole, –pyrone, and –carbamic acid adducts from Alstonia angustifolia. Tetrahedron, 66, 77997806.

[2] Kam TS, Jayashankar R, Sim KM, Yoganathan K. (1997) Angustimaline, an unusual nitrogenous compound from Alstonia angustifolia. Tetrahedron Letters, 38, 477478.

[3] Kam TS, Choo YM, Komiyama K. (2004) Unusual spirocyclic macroline alkaloids, nitrogenous derivatives, and a cytotoxic bisindole from Alstonia. Tetrahedron, 60, 39573966.

[4] Ghedira K, Zeches-Hanrot M, Richard B, Massiot G, Le Men-Olivier L, Sevenet T, Goh SH. (1988) Alkaloids of Alstonia angustifolia. Phytochemistry, 27, 39553962.

[5] Kam TS, Iek IH, Choo YM. (1999) Alkaloids from the stem-bark of Alstonia macrophylla. Phytochemistry, 51, 839844. [6] Kam TS, Choo YM. (2004) Alkaloids from Alstonia angustifolia. Phytochemistry, 65, 603608. [7] Kam TS, Choo YM. (2004) New indole alkaloids from Alstonia macrophylla. Journal of Natural Products, 67, 547552. [8] Kam TS, Choo YM. (2000) Novel macroline oxindoles from a Malayan Alstonia. Tetrahedron, 56, 61436150. [9] Wong WH, Lim PB, Chuah CH. (1996) Oxindole alkaloids from Alstonia macrophylla. Phytochemistry, 41, 313315. [10] Atta-ur-Rahman, Qureshi MM, Muzaffar A, De Silva KTD. (1988) Isolation and structural studies on the alkaloids of Alstonia macrophylla.

Heterocycles, 27, 725732. [11] Kam TS, Tan PS. (1990) Plumeran alkaloids from Kopsia profunda. Phytochemistry, 29, 23212322.

Natural Product Communications Vol. 7 (6) 2012 Published online (www.naturalproduct.us)

cis-Aconitic Anhydride Ethyl Ester and Phenolic Compounds from the Seeds of Alisma orientale Ming Zhao, Jing-ying Chen, Li-jia Xu, Tanja Goedecke, Xiao-qi Zhang, Jin-ao Duan and Chun-tao Che 785

Suppression of Nitric Oxide Synthase by Thienodolin in Lipopolysaccharide-stimulated RAW 264.7 Murine Macrophage Cells Eun-Jung Park, John M. Pezzuto, Kyoung Hwa Jang, Sang-Jip Nam, Sergio A. Bucarey and William Fenical 789

Review/Account Structural Characterization and Biological Effects of Constituents of the Seeds of Alpinia katsumadai (Alpina Katsumadai Seed) Joo-Won Nam and Eun-Kyoung Seo 795

Inventory, Constituents and Conservation of Biologically Important Sumatran Plants Dayar Arbain 799

Herbal Medicine in Healthcare-An Overview Mohammed Mosihuzzaman 807

Natural Product Communications 2012

Volume 7, Number 6

Contents

Original Paper Page

Distribution of Drimane Sesquiterpenoids and Tocopherols in Liverworts, Ferns and Higher Plants: Polygonaceae, Canellaceae and Winteraceae Species Yoshinori Asakawa, Agnieszka Ludwiczuk, Liva Harinantenaina, Masao Toyota, Mayumi Nishiki, Alicia Bardon and Kaeko Nii 685

A Novel Isopimarane Diterpenoid with Acetylcholinesterase Inhibitory Activity from Nepeta sorgerae, an Endemic Species to the Nemrut Mountain Anıl Yılmaz, Pınar Çağlar, Tuncay Dirmenci, Nezhun Gören and Gülaçtı Topçu 693

Synthesis of Taxane ABC Tricyclic Skeleton from Lycoctonine Xiao-Xia Liang, Pei Tang, Qiao-Hong Chen and Feng-Peng Wang 697

Two Antiproliferative Saponins of Tarenna grevei from the Madagascar Dry Forest Liva Harinantenaina, Peggy J. Brodie, Martin W. Callmander, L. Jérémie Razafitsalama, Vincent E. Rasamison, Etienne Rakotobe and David G. I. Kingston 705

Revisit to 25R/25S Stereochemical Analysis of Spirostane-type Steroidal Sapogenins and Steroidal Saponins via 1H NMR Chemical Shift Data Pawan K. Agrawal, Torsten Burkholz and Claus Jacob 709

Structure-Cardiac Activity Relationship of C19-Diterpenoid Alkaloids Xi-Xian Jian, Pei Tang, Xiu-Xiu Liu, Ruo-Bing Chao, Qiao-Hong Chen, Xue-Ke She, Dong-Lin Chen and Feng-Peng Wang 713

Unusual Reactions of a 7,17-seco-type C19-Diterpenoid Alkaloid Derived from Deltaline Ling Wang, Qiao-Hong Chen, and Feng-Peng Wang 721

Cytotoxic and Anti-HIV Phenanthroindolizidine Alkaloids from Cryptocarya chinensis Tian-Shung Wu, Chung-Ren Su and Kuo-Hsiung Lee 725

New Indole Alkaloid from Peschiera affinis (Apocynaceae) Allana Kellen L. Santos, Luciana L. Machado, Ayla Marcia C. Bizerra, Francisco José Q. Monte, Gilvandete M. P. Santiago, Raimundo Braz-Filho and Telma L. G. Lemos 729

Indole Alkaloids from Vinca major and V. minor Growing in Turkey Fatemeh Bahadori, Gülaçtı Topçu, Mehmet Boğa, Ayla Türkekul, Ufuk Kolak and Murat Kartal 731

Determination of the Absolute Configuration of 19-OH-(-)-eburnamonine Using a Combination of Residual Dipolar Couplings, DFT Chemical Shift Predictions, and Chiroptics Pablo Trigo-Mouriño, Roxana Sifuentes, Armando Navarro-Vázquez, Chakicherla Gayathri, Helena Maruenda and Roberto R. Gil 735

Unusual Nitrogenous Derivatives from Alstonia Shin-Jowl Tan, G. Subramaniam, Noel F. Thomas and Toh-Seok Kam 739

Photoactivated [3+2] Addition of 6,7-seco-angustilobine B to Fullerene [C60] Allan Patrick G. Macabeo, Dietmar Gehle, Karsten Krohn, Scott G. Franzblau and Alicia M. Aguinaldo 743

Flavone C-glycosides from Anthurium andraeanum Benjamin R. Clark, Jon Y. Suzuki, Barbara J. Bliss and Robert P. Borris 747

LC-PDA-ESI/MS Identification of the Phenolic Components of Three Compositae Spices: Chamomile, Tarragon, and Mexican Arnica Long-Ze Lin and James M. Harnly 749

Cinnamoylphenethyl Amides from Polygonum hyrcanicum Possess Anti-Trypanosomal Activity Fahimeh Moradi-Afrapoli, Nargues Yassa, Stefanie Zimmermann, Soodabeh Saeidnia, Abbas Hadjiakhoondi, Samad N. Ebrahimi and Matthias Hamburger 753

Comparative Study of the in vitro Bioactivities of Bupleurum rigidum and B. fruticescens Jose M. Prieto, Makanjuola O. Ogunsina, Andrea Novak, Amit Joshi, Judit Kokai, Ines Da Costa Rocha and Manuel Pardo de Santayana 757

Influence of Nutrient Medium Composition on in vitro Growth, Polyphenolic Content and Antioxidant Activity of Alchemilla mollis Marina Stanilova, Rossen Gorgorov, Antoaneta Trendafilova, Milena Nikolova and Antonina Vitkova 761

Saracoside: A New Lignan Glycoside from Saraca indica, a Potential Inhibitor of DNA Topoisomerase IB

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